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Past trauma, future breakthrough? - Epigenetics

Have you ever known a pair of identical twins? In their youths, they may have been impossible to tell apart. When they aged, however, they may have become more and more distinct, as the passage of time caused one twin to age much more quickly than his or her sibling. Epigenetics, a relatively new field of biology, has set out to account for these differences. Although identical twins share the same genetic code, the theory goes, differences in environment and living habits can influence a person’s health, speeding up or slowing down the aging process accordingly.

Perhaps more revolutionary are recent discoveries suggesting the influences these factors exert on an individual can actually be passed down to the next generation. This potential gives an added weight to the choices we make, which could theoretically affect not only ourselves, but also our offspring. While this idea of epigenetic inheritance has opened the doors for a range of innovative therapies, it has been met with criticism in the scientific community. It is difficult to believe that such a powerful mechanism could have eluded geneticists for so many years.

What is Epigenetics?

All the cells in an organism contain the same genome, and yet not all cells are created equal. Different genes are activated depending on the specific function of a cell, known as its differentiation. The epigenome is what allows cells to differentiate. It is the physical structure surrounding DNA, made up of chemical tags, which allows some genes to be expressed while others are silenced. A study in the New England Journal of Medicine describes the genome as written in pen, while the epigenome is written in pencil. It is flexible, changing in response to stress, diet, and other environmental signals.

The epigenome tweaks gene expression to optimize cell function. One way to accomplish this is through the addition of methyl groups, which are usually associated with gene inactivation. When a gene is tagged, or methylated, it is silenced and no longer produces protein. Roughly 10-20% of genes in a cell are active at a given time. In most cases, the epigenome is replicated along with the DNA. When it comes time to reproduce, almost all epigenetic tags are erased from the sperm and eggs so that the new embryo can start fresh. Tags that are not erased are said to be imprinted, and these will likely be present in the new organism.

Epigenetic Inheritance

While epigenetic inheritance is a compelling theory, it is notoriously difficult to demonstrate. Most successful studies have heretofore focused on animal models, with some notable exceptions. The Genetic Science Learning Center at the University of Utah cites several struggles that scientists must confront. First, they must rule out the possibility that a mutation in the genome is the underlying cause. Direct exposure to an environmental toxin must be excluded as well. This can be tricky, since when a mother is pregnant, there are three generations (the mother, the fetus, and the fetus’ reproductive cells) present at once. Finally, the epigenome is not fixed, which can make it difficult to pin down specific changes. The overwhelming number of variables makes confirming epigenetic inheritance a tall order, although some promising new studies have supported the concept.

A classic display of epigenetic inheritance centered on the parenting habits of mother rats. Rats who displayed nurturing behavior such as licking their young yielded offspring who were relatively resilient to stress. The young who were neglected as pups, on the other hand, were much more susceptible to anxiety as adults. In a majority of cases, whichever behavior a female rat was accustomed to as a pup became her modus operandi as a parent. After ruling out genetic factors, the scientists concluded that the experience of being licked as a pup had altered the rats’ epigenomes in a way that could be passed onto future generations.

Last month, a study was published describing the stress hormone profiles of Holocaust victims and their children. Holocaust survivors were more likely to have lower levels of cortisol, a hormone that helps the body deal with stress, in addition to an enzyme that helps break up cortisol in the blood. While their children’s cortisol levels were similarly low, the cortisol-deactivating enzyme levels were high. This latter trait is thought to be a defense mechanism that would have developed in utero, and may make the children of Holocaust survivors particularly susceptible to PTSD.

Taken together, these studies highlight an important aspect of the theory of inheritance: it can operate postnatally, in utero, or at the embryonic level.

Epigenetic Therapy

As scientists continue to learn about epigenetics, potential therapeutic uses are in the works. It may one day be possible to map a patient’s epigenome to create a customized nutritional plan, an idea known as nutrigenomics. Several disorders associated with intellectual disability involve epigenetic changes, which we may one day combat with targeted therapy.

Behavioral epigenetics is a new field that is concerned with the impact of epigenetic changes on human behavior. Scientists looked at methylation patterns in the brains of child abuse victims, finding a strong correlation between heavy methylation and a heightened risk for suicide. There is also potential that epigenetics could provide answers concerning behavioral disorders with a significant non-genetic component, such as schizophrenia.

The first disease ever traced to epigenetic changes was cancer, in 1983. Improper methylation patterns are a common symptom of tumors: depending on whether the wrong genes are tagged or untagged, this can cause rapid growth, chromosome instability, a breakdown in DNA repair, or a faulty self-destruct switch. Scientists are studying targeted drug therapies to fix these anomalies, a highly fragile process. Any treatment must be specific to the problematic cells alone, or risk causing the very disease it is intended to cure.

The excitement surrounding this field is contagious. Once you start looking beyond the genome, the options seem limitless. More reproducible testing will be required for epigenetic inheritance to be commonly accepted in the scientific community. It is unclear whether the results of past animal studies will carry over to humans as cleanly as some scientists hope. Further testing is imminent, however, as the implications are enormous.